Ultradense Array of On-Chip Sensors for High-Throughput Electrochemical Analyses.

High-throughput sensors are valuable tools for enabling massive, fast, and accurate diagnostics. To yield this type of electrochemical device in a simple and low-cost way, high-density arrays of vertical gold thin-film microelectrode-based sensors are demonstrated, leading to the rapid and serial interrogation of dozens of samples (10 µL droplets). Based on 16 working ultramicroelectrodes (UMEs) and 3 quasi-reference electrodes (QREs), a total of 48 sensors were engineered in a 3D crossbar arrangement that devised a low number of conductive lines. By exploiting this design, a compact chip (75 × 35 mm) can enable performing 16 sequential analyses without intersensor interferences by dropping one sample per UME finger. In practice, the electrical connection to the sensors was achieved by simply switching the contact among WE adjacent fingers. Importantly, a short analysis time was ensured by interrogating the UMEs with chronoamperometry or square wave voltammetry using a low-cost and hand-held one-channel potentiostat. As a proof of concept, the detection of Staphylococcus aureus in 15 samples was performed within 14 min (20 min incubation and 225 s reading). Additionally, the implementation of peptide-tethered immunosensors in these chips allowed the screening of COVID-19 from patient serum samples with 100% accuracy. Our experiments also revealed that dispensing additional droplets on the array (in certain patterns) results in the overestimation of the faradaic current signals, a phenomenon referred to as crosstalk. To address this interference, a set of analyses was conducted to design a corrective strategy that boosted the testing capacity by allowing using all on-chip sensors to address subsequent analyses (i.e., 48 samples simultaneously dispensed on the chip). This strategy only required grounding the unused rows of QRE and can be broadly adopted to develop high-throughput UME-based sensors. In practice, we could analyze 48 droplets (with [Fe(CN)6]4-) within ∼8 min using amperometry.

Ultradense Electrochemical Chips with Arrays of Nanostructured Microelectrodes to Enable Sensitive Diffusion-Limited Bioassays.

Nanostructured microelectrodes (NMEs) are an attractive alternative to yield sensitive bioassays in unprocessed samples. However, although valuable for different applications, nanoporous NMEs usually cannot boost the sensitivity of diffusion-limited analyses because of the enlarged Debye length within the nanopores, which reduces their accessibility. To circumvent this limitation, nanopore-free gold NMEs were electrodeposited from 45 µm SU-8 apertures, featuring nanoridged microspikes on a recessed surface of gold thin film while carrying interconnected crown-like and spiky structures along the edge of a SU-8 passivation layer. These structures were grown onto ultradense, vertical array chips that offer a promising strategy for translating reproducible, high-resolution, and cost-effective sensors into real-world applications. The NMEs yielded reproducible analyses, while machine learning allowed us to predict the analytical responses from NME electrodeposition data. By taking advantage of the high surface area and accessible structure of the NMEs, these structures provided a sensitivity for [Fe(CN)6]3-/4- that was 5.5× higher than that of bare WEs while also delivering a moderate antibiofouling property in undiluted human plasma. As a proof of concept, these electrodes were applied toward the fast (22 min) and simple determination of Staphylococcus aureus by monitoring the oxidation of [Fe(CN)6]4-, which acted as a cellular respiration rate redox reporter. The sensors also showed a wide dynamic range, spanning 5 orders of magnitude, and a calculated limit of detection of 0.2 CFU mL-1.

Single-Response Duplexing of Electrochemical Label-Free Biosensor from the Same Tag.

Multiplexing is a valuable strategy to boost throughput and improve clinical accuracy. Exploiting the vertical, meshed design of reproducible and low-cost ultra-dense electrochemical chips, the unprecedented single-response multiplexing of typical label-free biosensors is reported. Using a cheap, handheld one-channel workstation and a single redox probe, that is, ferro/ferricyanide, the recognition events taking place on two spatially resolved locations of the same working electrode can be tracked along a single voltammetry scan by collecting the electrochemical signatures of the probe in relation to different quasi-reference electrodes, Au (0 V) and Ag/AgCl ink (+0.2 V). This spatial isolation prevents crosstalk between the redox tags and interferences over functionalization and binding steps, representing an advantage over the existing non-spatially resolved single-response multiplex strategies. As proof of concept, peptide-tethered immunosensors are demonstrated to provide the duplex detection of COVID-19 antibodies, thereby doubling the throughput while achieving 100% accuracy in serum samples. The approach is envisioned to enable broad applications in high-throughput and multi-analyte platforms, as it can be tailored to other biosensing devices and formats.

Machine learning toward high-performance electrochemical sensors.

The so-coined fourth paradigm in science has reached the sensing area, with the use of machine learning (ML) toward data-driven improvements in sensitivity, reproducibility, and accuracy, along with the determination of multiple targets from a single measurement using multi-output regression models. Particularly, the use of supervised ML models trained on large data sets produced by electrical and electrochemical bio/sensors has emerged as an impacting trend in the literature by allowing accurate analyses even in the presence of usual issues such as electrode fouling, poor signal-to-noise ratio, chemical interferences, and matrix effects. In this trend article, apart from an outlook for the coming years, we present examples from the literature that demonstrate how helpful ML algorithms can be for dispensing the adoption of experimental methods to address the aforesaid interfering issues, ultimately contributing to translate testing technologies into on-site, practical, and daily applications.

Balance Exercise Circuit for fall prevention in older adults: a randomized controlled crossover trial.

Objectives: This study aimed to assess the immediate and short-term effects of the Balance Exercise Circuit (BEC) on muscle strength, postural balance, and quality of life, with the aim of preventing falls in older adults. Methods: Twenty-two volunteers participated in this randomized controlled crossover study. Group A performed BEC training in the initial 3 months and received no intervention in the following 3 months. Group B received no intervention during the first 3 months and then participated in BEC training for the next 3 months. In addition, participants were followed for an additional 3 months. Muscle strength, postural balance, functional mobility, and quality of life were assessed, respectively, using an isokinetic dynamometer, force platform, TUG test, and the WHOQOL. Results: After 3 months of training, Group A presented improved balance and rate of force development (RFD), while Group B presented improvements in RFD, TUG performance, and WHOQOL physical and psychological domains. Regarding the short-term effects, the participants maintained the training effects in WHOQOL balance, RFD, and the social domain. In addition, the number of falls decreased during follow-up. Conclusion: The BEC intervention improved muscle strength, postural balance, and quality of life in older adults, in addition to reducing the risk of falls. Trial registration: Brazilian Registry of Clinical Trials (ReBEC) - RBR-5nvrwm.

Urinary Continence in German and Brazilian Individuals With Spina Bifida: Influence of Intermittent Catheterization.

PURPOSE: The purpose of this study was to identify the factors associated with acquisition of urinary continence following introduction of intermittent catheterization (IC). STUDY DESIGN: Cross-sectional study. SUBJECTS AND SETTING: The study sample comprised 104 females and 84 males. Their median age was 11 years (interquartile range = 6.0-22.0 years). Data were collected in 2 settings, the Rehabilitation Hospital in Belo Horizonte Brazil and Dortmund University North-Rhine, Westphalia, Germany. METHODS: Ninety-four Brazilian and 94 German individuals who had experienced IC participated in the study. Data were collected using printed (Brazil) and online (Germany) questionnaires and analyzed using multivariate logistical regression and analysis of variance. RESULTS: Out of the 188 participants, 62.2% (117) achieved complete or partial continence. We found that increasing the frequency of IC increases the likelihood that the patient will acquire continence with IC. Using self-catheterization can increase the likelihood of acquiring continence (partial or complete) up to 2.9 times, in relation to someone who uses no self-catheterization. CONCLUSIONS: Among patients with spina bifida and neurogenic bladder dysfunction, acquisition of urinary continence after initiating IC was influenced by the use of self-catheterization and daily frequency of IC.

Effect of equine-assisted therapy on the postural balance of the elderly.

OBJECTIVE: To determine whether equine-assisted therapy (hippotherapy) produces alterations in the balance of the elderly. METHODS: The sample included 17 older adults who were divided into experimental (7 subjects) and control (10 subjects) groups. Stabilometry data were acquired with a force platform. The Timed Up and Go test (TUG) was used for clinical analysis of seated balance, transfer from a seated to a standing position, walking stability and changes in gait. Sixteen equine-assisted therapy sessions were carried out. RESULTS: Mann-Witney was used to compare the means between groups and no significant differences were found in the analyzed stabilometric parameters. In intragroup comparison with the Wilcoxon test, a significant increase in the variables COPy and Area (p=0.02) was observed. Equine-assisted therapy significantly affected (p=0.04) TUG test means between the experimental and control groups (Mann-Witney). Intragroup TUG test means were also significantly affected (p=0.04) according to the Wilcoxon test. CONCLUSIONS: Because senescence tends to normalize stabilometric measures, the number of equine-assisted therapy sessions was insufficient to determine any differences. Nevertheless, the significant improvement in TUG test scores demonstrates that this treatment frequency was a predictor of reduced fall risk in the elderly. Article registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) under number ACTRN12610000534088.

Effect of equine-assisted therapy on the postural balance of the elderly / Efeito da equoterapia no equilíbrio postural de idosos

OBJECTIVE: To determine whether equine-assisted therapy (hippotherapy) produces alterations in the balance of the elderly. METHODS: The sample included 17 older adults who were divided into experimental (7 subjects) and control (10 subjects) groups. Stabilometry data were acquired with a force platform. The Timed Up and Go test (TUG) was used for clinical analysis of seated balance, transfer from a seated to a standing position, walking stability and changes in gait. Sixteen equine-assisted therapy sessions were carried out. RESULTS: Mann-Witney was used to compare the means between groups and no significant differences were found in the analyzed stabilometric parameters. In intragroup comparison with the Wilcoxon test, a significant increase in the variables COPy and Area (p=0.02) was observed. Equine-assisted therapy significantly affected (p=0.04) TUG test means between the experimental and control groups (Mann-Witney). Intragroup TUG test means were also significantly affected (p=0.04) according to the Wilcoxon test. CONCLUSIONS: Because senescence tends to normalize stabilometric measures, the number of equine-assisted therapy sessions was insufficient to determine any differences. Nevertheless, the significant improvement in TUG test scores demonstrates that this treatment frequency was a predictor of reduced fall risk in the elderly. Article registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) under number ACTRN12610000534088.

OBJETIVO: Verificar se a equoterapia é capaz de produzir alterações no equilíbrio de idosos. MÉTODOS: Desenvolveu-se um estudo experimental controlado. A amostra foi composta de 17 idosos, divididos em grupo experimental (GE), sete sujeitos e grupo controle (GC), dez sujeitos. A aquisição dos dados da estabilometria foi realizada por meio da plataforma de força da marca AMTI (Force Measurement Systems). Para análise clínica do equilíbrio sentado, transferências de sentado para a posição em pé, estabilidade na deambulação e mudanças do curso da marcha, utilizou-se o teste Timed Up and Go (TUG). Foram realizadas 16 sessões de equoterapia. RESULTADOS: Na comparação das médias entre os grupos por meio do teste de Mann-Whitney, não houve diferença significativa nos parâmetros estabilométricos analisados. Já na comparação das médias intragrupo por meio do teste de Wilcoxon, verificou-se aumento significante sobre as variáveis COPy e área (p=0,02). Nas médias entre o GE e o GC, por meio do teste de Mann-Whitney para análise do teste TUG, verificou-se efeito significante (p=0,04) da equoterapia. Na comparação das médias intragrupo pelo teste de Wilcoxon, verificou-se efeito significante (p=0,04) sobre a variável TUG. CONCLUSÕES: A senescência tende a normalizar as medidas estabilométricas, sendo insuficiente, com esse número de sessões de equoterapia, apontar diferenças ligadas a essa intervenção. No entanto, essa frequência de tratamento foi suficiente como preditor de menor risco de quedas em idosos, uma vez que o teste de TUG mostrou diminuição significativa do tempo necessário para executá-lo. Artigo registrado no Australian New Zealand Clinical Trials Registry (ANZCTR) sob o número ACTRN12610000534088.